The following description is provided to assist the understanding of the reader. None of the information provided or references cited herein are admitted to be prior art to the present technology.
4-Amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one has the structure shown in Formula I:

The compound of Formula I inhibits various protein kinases, such as tyrosine receptor protein kinase inhibitors. Consequently, the compound of Formula I and its salts are useful for inhibiting angiogenesis and treating cancers such as multiple myeloma (MM), acute myelogenous leukemia (AML), prostate cancer, breast cancer, renal cancer, colon cancer, and melanoma. Use and preparation of this compound and its salts, including the mono-lactic acid salt, are described in U.S. Pat. Nos. 6,605,617, 6,774,237, 7,335,774, and 7,470,709, and in U.S. patent application Ser. Nos. 10/982,757, 10/982,543, and 10/706,328, and in the published PCT applications WO2006/127926, published on Nov. 30, 2006 and WO2009/115562 published on Sep. 24, 2009, each of which is incorporated herein by reference in its entirety.
The monolactate salt of the compound of Formula I exists in a variety of polymorphs, including, e.g., the monohydrate Form B and the anhydrous Form II. Polymorphs occur where the same composition of matter (including its hydrates and solvates) crystallizes in a different lattice arrangement resulting in different thermodynamic and physical properties specific to the particular crystalline form. Because physical properties of polymorphs can vary markedly and may affect the biological properties of a drug (e.g., bioavailability), it is important to be able to reliably produce a drug such as the compound of Formula I with little or no contamination by other polymorphs. The aim of the present invention is to provide such a process of preparing a polymorphic form of the lactic acid salt of 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one.